The development of biological tools to aid in the genetic investigation of the black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros mitochondrial genomes
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
- Date Issued: 2015
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
- Date Issued: 2015
Three new pentacyclic triterpenoids from twigs of Manniophyton fulvum (Euphorbiaceae)
- Mbeunkeu, Ahri B D, Noundou, Xavier S, Krause, Rui W M, Teinkela, Jean E M, Laatsch, Hartmut, Azebaze, Anatole G B, Vardamides, Juliette C, Tala, Michel F
- Authors: Mbeunkeu, Ahri B D , Noundou, Xavier S , Krause, Rui W M , Teinkela, Jean E M , Laatsch, Hartmut , Azebaze, Anatole G B , Vardamides, Juliette C , Tala, Michel F
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126782 , vital:35922 , https://doi.org/10.1016/j.phytol.2018.06.019
- Description: Phytochemical investigation of the methanol extracts of the twigs of Manniophyton fulvum has led to the isolation and characterization of three new pentacyclic triterpenoids, designated as 3α,28-dihydroxyfriedelan-1-one (1), manniotaraxerol A (3) and manniotaraxerol B (4), along with fourteen known compounds, 3α-hydroxy-1-oxofriedelane (2), betulinic acid (5), friedelin (S1), taraxerol (S2), a mixture of stigmasterol (S3) and β-sitosterol (S4), herranone (S5), docosanoic acid (S6), ursolic acid (S7), nasutin B (S8), bergenin (S9), stigmasterol-3-O-β-Dglucopyranoside (S10), 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)glycerol (S11), and aridanin (S12). The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI and ESI-MS). 3α,28-Dihydroxyfriedelan-1-one (1), 3α-hydroxy-1-oxofriedelane (2), manniotaraxerol A (3), manniotaraxerol B (4), and betulinic acid (5) were evaluated against HeLa (human cervix adenocarcinoma) cancer cells. Manniotaraxerol A (3) showed weak in vitro cytotoxicity with a cell viability value of 49.3%. Betulinic acid (5) also showed significant cytotoxicity against HeLa cell with a cell viability value of 4.0%; the other compounds were inactive in this test.
- Full Text:
- Date Issued: 2018
- Authors: Mbeunkeu, Ahri B D , Noundou, Xavier S , Krause, Rui W M , Teinkela, Jean E M , Laatsch, Hartmut , Azebaze, Anatole G B , Vardamides, Juliette C , Tala, Michel F
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126782 , vital:35922 , https://doi.org/10.1016/j.phytol.2018.06.019
- Description: Phytochemical investigation of the methanol extracts of the twigs of Manniophyton fulvum has led to the isolation and characterization of three new pentacyclic triterpenoids, designated as 3α,28-dihydroxyfriedelan-1-one (1), manniotaraxerol A (3) and manniotaraxerol B (4), along with fourteen known compounds, 3α-hydroxy-1-oxofriedelane (2), betulinic acid (5), friedelin (S1), taraxerol (S2), a mixture of stigmasterol (S3) and β-sitosterol (S4), herranone (S5), docosanoic acid (S6), ursolic acid (S7), nasutin B (S8), bergenin (S9), stigmasterol-3-O-β-Dglucopyranoside (S10), 1,2-di-O-palmitoyl-3-O-(6-sulfo-α-D-quinovopyranosyl)glycerol (S11), and aridanin (S12). The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR, EI and ESI-MS). 3α,28-Dihydroxyfriedelan-1-one (1), 3α-hydroxy-1-oxofriedelane (2), manniotaraxerol A (3), manniotaraxerol B (4), and betulinic acid (5) were evaluated against HeLa (human cervix adenocarcinoma) cancer cells. Manniotaraxerol A (3) showed weak in vitro cytotoxicity with a cell viability value of 49.3%. Betulinic acid (5) also showed significant cytotoxicity against HeLa cell with a cell viability value of 4.0%; the other compounds were inactive in this test.
- Full Text:
- Date Issued: 2018
The crystal and molecular structure of the bis(4-N, N1-dimethylaminopyridine) solvate of disalicylicacidatobis(nitrotodioxouranium)(VI)
- Nassimbeni, L R, Rodgers, Allen L, Haigh, John M
- Authors: Nassimbeni, L R , Rodgers, Allen L , Haigh, John M
- Date: 1976
- Language: English
- Type: text , Article
- Identifier: vital:6415 , http://hdl.handle.net/10962/d1006526
- Description: The structure of the title compound [(C7H4NO8U)(C7H11N2)]2 has been determined by Patterson and Fourier methods from single crystal X-ray diffraction data collected on a four-circle diffractometer. Full-matrix least-squares refinement yielded a final conventional R of 0.041 for 2189 reflections. The complex crystallizes in the space group P with a = 11.004(5), b = 9.981(5), c = 9.928(5) Å, α = 119.6(3), β = 107.7(3), γ = 81.9(3)°, Dm = 2.17, Dc = 2.173g cm−3. The structure is dimeric. The uranium atoms are eight-coordinate and are bridged via centrosymmetrically related carboxylic oxygen atoms. The nitrate group is bidentate and the average U---O (ligand) distance is 2.463 Å. Hydrogen bonding of the type N---HO links two dimethyl-aminopyridine molecules to the dimer.
- Full Text:
- Date Issued: 1976
- Authors: Nassimbeni, L R , Rodgers, Allen L , Haigh, John M
- Date: 1976
- Language: English
- Type: text , Article
- Identifier: vital:6415 , http://hdl.handle.net/10962/d1006526
- Description: The structure of the title compound [(C7H4NO8U)(C7H11N2)]2 has been determined by Patterson and Fourier methods from single crystal X-ray diffraction data collected on a four-circle diffractometer. Full-matrix least-squares refinement yielded a final conventional R of 0.041 for 2189 reflections. The complex crystallizes in the space group P with a = 11.004(5), b = 9.981(5), c = 9.928(5) Å, α = 119.6(3), β = 107.7(3), γ = 81.9(3)°, Dm = 2.17, Dc = 2.173g cm−3. The structure is dimeric. The uranium atoms are eight-coordinate and are bridged via centrosymmetrically related carboxylic oxygen atoms. The nitrate group is bidentate and the average U---O (ligand) distance is 2.463 Å. Hydrogen bonding of the type N---HO links two dimethyl-aminopyridine molecules to the dimer.
- Full Text:
- Date Issued: 1976
The Formation of 2, 2, 4-Trimethyl-2, 3-dihydro-1 H-1, 5-Benzodiazepine from 1, 2-Diaminobenzene in the Presence of Acetone
- Odame, Felix, Kleyi, Phumelele, Hosten, Eric C, Betz, Richard, Lobb, Kevin A, Tshentu, Zenixole R
- Authors: Odame, Felix , Kleyi, Phumelele , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448952 , vital:74773 , xlink:href="https://doi.org/10.3390/molecules181114293"
- Description: In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed.
- Full Text:
- Date Issued: 2013
- Authors: Odame, Felix , Kleyi, Phumelele , Hosten, Eric C , Betz, Richard , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2013
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/448952 , vital:74773 , xlink:href="https://doi.org/10.3390/molecules181114293"
- Description: In an attempt to synthesize a 2-substituted benzimidazole from the reaction of o-phenylenediamine and isophthalic acid in the presence of acetone and ethanol under microwave irradiation, a salt of the isophthalate ion and 2,2,4-trimethyl-2,3-dihydro-1H-1,5-benzodiazepin-5-ium ion was obtained. The condensation of two moles of acetone with the amine groups resulted in the formation of the benzodiazepine which crystallized as an iminium cation forming a salt with the isophthalate anion. The formation of benzodiazepine was also confirmed by performing the reaction of o-phenylenediamine with excess acetone in ethanol under conventional heating conditions. The compounds were characterized by NMR, FTIR, HRMS and microanalysis as well as X-ray crystallography. The reaction mechanism leading to the formation of benzodiazepine is also discussed.
- Full Text:
- Date Issued: 2013
The synthesis, empirical and theoretical studies of various (N→B) diarylborinate esters
- Authors: Manana, Pholani Sakhile
- Date: 2021-12
- Subjects: Port Elizabeth (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/53869 , vital:46027
- Description: A series of core-functionalized borinic acids was synthesized from Grignard reagents and tributylborate and reacted with ethanolamine, amino acids, 2-pyridylmethanol as well as 2-(ethyl amino ethanol). Among the borinic acids synthesized were the ones bearing: para-(2, 15, 16, 22, 27)-methyl, (3, 20, 25)-chloro, (4, 23, 26)-fluoro, (5)-methoxy; meta-(7, 17)-methyl, (9)-fluoro; ortho-(6)-methyl, (8)-chloro, (10, 18, 19)-methoxy substituents on their respective aromatic systems. All compounds obtained by condensation of the borinic acids with the aforementioned nitrogen-containing substrates were characterized structurally by means of diffraction studies based on single crystals and found to constitute chelate esters/amides featuring covalent B-O and dative N→B bonds. The chelate compounds researched in this study could be classified into four families and represent the compounds: ethanol amine: (1) 2,2-diphenyl-1,3,2-oxazaborolidines, (2) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (3) 2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (4) 2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (5) 2,2-bis(p-methoxyphenyl)-1,3,2-oxazaborolidines, (6) 2,2-bis(o-tolyl)-1,3,2-oxazaborolidines, (7) 2,2-bis(m-tolyl)-1,3,2-oxazaborolidines, (8) 2,2-bis(o-chlorophenyl)-1,3,2-oxazaborolidines, (9) 2,2-bis(m-fluorophenyl)-1,3,2-oxazaborolidines, (10) 2,2-bis(o-methoxyphenyl)-1,3,2-oxazaborolidines. α-amino acids : (14) 4-methyl-2,2-diphenyl-1,3,2-oxazaborolidin-5-ones, (15) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (16) 4-methyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (17) 4-isopropyl-2,2-bis(m-tolyl)-1,3,2-oxazaborolidin-5-ones, (18) 4-methyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (19) 4-acetamidyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (20) 4-phenylethane-2,2-bis(p-chlorophenyl)-1,3,2 oxazaborolidin-5-ones. 2-pyridylmethanol: (21) 1,3-hydroxypyridyl-2,2-diphenyl 1,3,2-oxazaborolidines, (22) 1,3-hydroxypyridyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (23) 1,3-hydroxypyridyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines 2-(ethyl amino ethanol): (24) 3-ethyl-2,2-diphenyl-1,3,2-oxazaborolidines, (25) 3-ethyl-2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (26) 3-ethyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (27) 3-ethyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines. Apart from structural studies in the solid state, the compounds were also characterized by means of multinuclear NMR spectroscopy (1H, 11B, 13C) as well as UV/vis and FTIR. The typical 11B resonances were found in the range of (4-10 ppm). A series of characteristic metrical parameters for the compounds in the solid state as well as typical NMR shifts for the chelate target molecules was established that allowed for the determination of the coordination induced shift. The carbon atom bonded to the oxygen atom shifted upfield, while the carbon atom bonded to the nitrogen atom shifted downfield. Factors mentioned in the literature that has an influence on the hydrolytic stability on the heterocyclic borinate motif have been taken into consideration and verified for the systems researched in this study. The substitution at the nitrogen atom with one ethyl group caused the greatest increases in the N→B bond length (27) 1.714 Å, due to the increase in the nitrogen Lewis basicity, making it the least hydrolytically stable, these include compounds (24-26). Furthermore, DFT calculations were performed by employing Becke’s three parameter hybrid exchange functional with Lee–Yang–Parr functional (B3LYP) method using the Gaussian 16 program package (Rev. B01) employing the basis set 6-311++G(d,p), to corroborate and correlate the experimental findings, which gave a general R-squared value of 0.9978 for calculated vs experimental 13C chemical shifts. Thermal properties are recorded for select compounds, indicating the ΔH and the melting points. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Full Text:
- Date Issued: 2021-12
- Authors: Manana, Pholani Sakhile
- Date: 2021-12
- Subjects: Port Elizabeth (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/53869 , vital:46027
- Description: A series of core-functionalized borinic acids was synthesized from Grignard reagents and tributylborate and reacted with ethanolamine, amino acids, 2-pyridylmethanol as well as 2-(ethyl amino ethanol). Among the borinic acids synthesized were the ones bearing: para-(2, 15, 16, 22, 27)-methyl, (3, 20, 25)-chloro, (4, 23, 26)-fluoro, (5)-methoxy; meta-(7, 17)-methyl, (9)-fluoro; ortho-(6)-methyl, (8)-chloro, (10, 18, 19)-methoxy substituents on their respective aromatic systems. All compounds obtained by condensation of the borinic acids with the aforementioned nitrogen-containing substrates were characterized structurally by means of diffraction studies based on single crystals and found to constitute chelate esters/amides featuring covalent B-O and dative N→B bonds. The chelate compounds researched in this study could be classified into four families and represent the compounds: ethanol amine: (1) 2,2-diphenyl-1,3,2-oxazaborolidines, (2) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (3) 2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (4) 2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (5) 2,2-bis(p-methoxyphenyl)-1,3,2-oxazaborolidines, (6) 2,2-bis(o-tolyl)-1,3,2-oxazaborolidines, (7) 2,2-bis(m-tolyl)-1,3,2-oxazaborolidines, (8) 2,2-bis(o-chlorophenyl)-1,3,2-oxazaborolidines, (9) 2,2-bis(m-fluorophenyl)-1,3,2-oxazaborolidines, (10) 2,2-bis(o-methoxyphenyl)-1,3,2-oxazaborolidines. α-amino acids : (14) 4-methyl-2,2-diphenyl-1,3,2-oxazaborolidin-5-ones, (15) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (16) 4-methyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (17) 4-isopropyl-2,2-bis(m-tolyl)-1,3,2-oxazaborolidin-5-ones, (18) 4-methyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (19) 4-acetamidyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (20) 4-phenylethane-2,2-bis(p-chlorophenyl)-1,3,2 oxazaborolidin-5-ones. 2-pyridylmethanol: (21) 1,3-hydroxypyridyl-2,2-diphenyl 1,3,2-oxazaborolidines, (22) 1,3-hydroxypyridyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (23) 1,3-hydroxypyridyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines 2-(ethyl amino ethanol): (24) 3-ethyl-2,2-diphenyl-1,3,2-oxazaborolidines, (25) 3-ethyl-2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (26) 3-ethyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (27) 3-ethyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines. Apart from structural studies in the solid state, the compounds were also characterized by means of multinuclear NMR spectroscopy (1H, 11B, 13C) as well as UV/vis and FTIR. The typical 11B resonances were found in the range of (4-10 ppm). A series of characteristic metrical parameters for the compounds in the solid state as well as typical NMR shifts for the chelate target molecules was established that allowed for the determination of the coordination induced shift. The carbon atom bonded to the oxygen atom shifted upfield, while the carbon atom bonded to the nitrogen atom shifted downfield. Factors mentioned in the literature that has an influence on the hydrolytic stability on the heterocyclic borinate motif have been taken into consideration and verified for the systems researched in this study. The substitution at the nitrogen atom with one ethyl group caused the greatest increases in the N→B bond length (27) 1.714 Å, due to the increase in the nitrogen Lewis basicity, making it the least hydrolytically stable, these include compounds (24-26). Furthermore, DFT calculations were performed by employing Becke’s three parameter hybrid exchange functional with Lee–Yang–Parr functional (B3LYP) method using the Gaussian 16 program package (Rev. B01) employing the basis set 6-311++G(d,p), to corroborate and correlate the experimental findings, which gave a general R-squared value of 0.9978 for calculated vs experimental 13C chemical shifts. Thermal properties are recorded for select compounds, indicating the ΔH and the melting points. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Full Text:
- Date Issued: 2021-12
Spectroscopic and nonlinear optical properties of the four positional isomers of 4α-(4-tert-butylphenoxy) phthalocyanine
- Ngubeni, Grace N, Britton, Jonathan, Mack, John, New, Edward, Hancox, Ian, Walker, Marc, Nyokong, Tebello, Jones, Tim S, Khene,Samson M
- Authors: Ngubeni, Grace N , Britton, Jonathan , Mack, John , New, Edward , Hancox, Ian , Walker, Marc , Nyokong, Tebello , Jones, Tim S , Khene,Samson M
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/241448 , vital:50940 , xlink:href="https://doi.org/10.1039/C5TC01601K"
- Description: The spectroscopic and nonlinear optical properties of the positional isomers of metal free 4α-(4-tert-butylphenoxy) phthalocyanine are presented. Second order nonlinear polarizability (β), imaginary hyperpolarizability (Im(γ)) and imaginary susceptibility (Im[χ(3)]) values were determined for the four positional isomers. The measured β values of the four isomers displayed the following trend, C4h (34.0 × 10−5 m MW−1) > D2h (28.8 × 10−5 m MW−1) > C2v (22.8 × 10−5 m MW−1) > Cs (13.7 × 10−5 m MW−1).
- Full Text:
- Date Issued: 2015
- Authors: Ngubeni, Grace N , Britton, Jonathan , Mack, John , New, Edward , Hancox, Ian , Walker, Marc , Nyokong, Tebello , Jones, Tim S , Khene,Samson M
- Date: 2015
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/241448 , vital:50940 , xlink:href="https://doi.org/10.1039/C5TC01601K"
- Description: The spectroscopic and nonlinear optical properties of the positional isomers of metal free 4α-(4-tert-butylphenoxy) phthalocyanine are presented. Second order nonlinear polarizability (β), imaginary hyperpolarizability (Im(γ)) and imaginary susceptibility (Im[χ(3)]) values were determined for the four positional isomers. The measured β values of the four isomers displayed the following trend, C4h (34.0 × 10−5 m MW−1) > D2h (28.8 × 10−5 m MW−1) > C2v (22.8 × 10−5 m MW−1) > Cs (13.7 × 10−5 m MW−1).
- Full Text:
- Date Issued: 2015
Isolation and Characterisation of Stigmasterol and β–Sitosterol from Anthocleista djalonensis A. Chev.
- Okoro, Ijeoma S, Tor-Anyiin, Terrumun A, Igoli, John O, Noundou, Xavier S, Krause, Rui W M
- Authors: Okoro, Ijeoma S , Tor-Anyiin, Terrumun A , Igoli, John O , Noundou, Xavier S , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126191 , vital:35857 , https://doi.org/10.9734/AJOCS/2017/37147
- Description: Aim: Anthocleista djalonensis A. Chev. is a plant with several chemical constituents whichaccounts for its ethno-pharmacological uses. The present study is aimed at identifying and characterizing the active principles from the roots of the plant. Place and Duration of Study: The study was carried out at the Department of Organic Chemistry,Rhodes University, Grahamstown, South Africa between March and July 2016. Methodology: The root powder was subjected to maceration with methanol to obtain the crude extract. The methanol extract was fractionated using hexane, ethyl acetate and acetone successively. The acetone extract was thereafter subjected to column chromatography to isolate any pure components. Results: White needle-like crystals were obtained which on spectral analysis(IR, 1H NMR, 13C NMR, 2D- NMR, and ESI-MS ) were identified as a mixture of stigmasterol and β-sitosterol. Conclusion: The compounds isolated were identified as stigmasterol and β-sitosterol.
- Full Text:
- Date Issued: 2018
- Authors: Okoro, Ijeoma S , Tor-Anyiin, Terrumun A , Igoli, John O , Noundou, Xavier S , Krause, Rui W M
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/126191 , vital:35857 , https://doi.org/10.9734/AJOCS/2017/37147
- Description: Aim: Anthocleista djalonensis A. Chev. is a plant with several chemical constituents whichaccounts for its ethno-pharmacological uses. The present study is aimed at identifying and characterizing the active principles from the roots of the plant. Place and Duration of Study: The study was carried out at the Department of Organic Chemistry,Rhodes University, Grahamstown, South Africa between March and July 2016. Methodology: The root powder was subjected to maceration with methanol to obtain the crude extract. The methanol extract was fractionated using hexane, ethyl acetate and acetone successively. The acetone extract was thereafter subjected to column chromatography to isolate any pure components. Results: White needle-like crystals were obtained which on spectral analysis(IR, 1H NMR, 13C NMR, 2D- NMR, and ESI-MS ) were identified as a mixture of stigmasterol and β-sitosterol. Conclusion: The compounds isolated were identified as stigmasterol and β-sitosterol.
- Full Text:
- Date Issued: 2018
Synthesis and in vitro biological studies of ursolic acid-based hybrid compounds
- Authors: Khwaza, Vuyolwethu
- Date: 2022
- Subjects: Herbal medicine , Herbs -- Therapeutic use , Antineoplastic antibiotics
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10353/27797 , vital:69689
- Description: Ursolic acid UA, a pentacyclic triterpenoid that is commonly found in many medicinal herbs and fruits, has been identified as a potential source of therapeutic agents because of its potent biological effects, which include its potential anticancer and antimicrobial activities. However, its limited solubility, rapid metabolism and poor bioavailability inhibit its clinical applications. Numerous UA derivatives have been prepared over the past years in an effort to mitigate the drawbacks associated with UA, as new chemical entities for the treatment of various infections. There is very little progress in the discovery of efficient UA derivatives. In this study, a class of ester and amide-linked ursolic acid-based hybrid compounds fused with selected pharmaceutical scaffolds were successfully synthesized using amidation and esterification reactions and tested for antibacterial and cytotoxicity activities. Hybridizing UA with other known pharmaceutical scaffolds has the potential of overcoming its drawbacks. FT-IR, Mass Spectroscopy, and 1H13C-NMR spectroscopy were used to confirm the structures of the synthesized hybrid compounds. Among the tested ester-linked hybrid compounds in Chapter three, compounds 3.14-3.19,3.21, 3.34, 3.31, and 3.30 demonstrated significant antibacterial activities against some tested bacteria, with MIC values of 15.625 μgml. Furthermore, the in vitro cytotoxicity of these hybrids was determined using the MTT assay against three human tumor cell lines MCF7, MDA-MB-231, and HeLa cells. Compounds 3.19 and 3.34 were found to have better cytotoxic activity when compared to ursolic acid, with IC50 values of 46.99 and 48.18 μg ml respectively. Both compounds revealed more promising docking results, presenting favourable binding interactions as well as better docking energy against the MCF 7 protein target compared to the parent compound ursolic acid. In Chapter Four, among the tested amide-linked hybrid compounds, Compounds 4.17 and 4.24 demonstrated significant antibacterial activity against the majority of bacterial strains with MIC values of 15.625 gml. Compound 4.24 exhibited a MIC value of 15.625gmL against BS, SA, PV, KO, PM, and EC. Compound 4.23 was more cytotoxic to HeLa cells than ursolic acid. Furthermore, molecular docking calculations revealed that compound 4.16 strongly binds to the protein epidermal growth factor receptor while e compounds 4.17 and 4.24 showed a strong binding affinity for the methionyl-tRNA synthetase. In both cases, the hybrid compounds showed better conformational fittings in the active site of the targeted proteins as compared to the parent ursolic acid. , Thesis (MSc) -- Faculty of Science and Agriculture, 2022
- Full Text:
- Date Issued: 2022
- Authors: Khwaza, Vuyolwethu
- Date: 2022
- Subjects: Herbal medicine , Herbs -- Therapeutic use , Antineoplastic antibiotics
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10353/27797 , vital:69689
- Description: Ursolic acid UA, a pentacyclic triterpenoid that is commonly found in many medicinal herbs and fruits, has been identified as a potential source of therapeutic agents because of its potent biological effects, which include its potential anticancer and antimicrobial activities. However, its limited solubility, rapid metabolism and poor bioavailability inhibit its clinical applications. Numerous UA derivatives have been prepared over the past years in an effort to mitigate the drawbacks associated with UA, as new chemical entities for the treatment of various infections. There is very little progress in the discovery of efficient UA derivatives. In this study, a class of ester and amide-linked ursolic acid-based hybrid compounds fused with selected pharmaceutical scaffolds were successfully synthesized using amidation and esterification reactions and tested for antibacterial and cytotoxicity activities. Hybridizing UA with other known pharmaceutical scaffolds has the potential of overcoming its drawbacks. FT-IR, Mass Spectroscopy, and 1H13C-NMR spectroscopy were used to confirm the structures of the synthesized hybrid compounds. Among the tested ester-linked hybrid compounds in Chapter three, compounds 3.14-3.19,3.21, 3.34, 3.31, and 3.30 demonstrated significant antibacterial activities against some tested bacteria, with MIC values of 15.625 μgml. Furthermore, the in vitro cytotoxicity of these hybrids was determined using the MTT assay against three human tumor cell lines MCF7, MDA-MB-231, and HeLa cells. Compounds 3.19 and 3.34 were found to have better cytotoxic activity when compared to ursolic acid, with IC50 values of 46.99 and 48.18 μg ml respectively. Both compounds revealed more promising docking results, presenting favourable binding interactions as well as better docking energy against the MCF 7 protein target compared to the parent compound ursolic acid. In Chapter Four, among the tested amide-linked hybrid compounds, Compounds 4.17 and 4.24 demonstrated significant antibacterial activity against the majority of bacterial strains with MIC values of 15.625 gml. Compound 4.24 exhibited a MIC value of 15.625gmL against BS, SA, PV, KO, PM, and EC. Compound 4.23 was more cytotoxic to HeLa cells than ursolic acid. Furthermore, molecular docking calculations revealed that compound 4.16 strongly binds to the protein epidermal growth factor receptor while e compounds 4.17 and 4.24 showed a strong binding affinity for the methionyl-tRNA synthetase. In both cases, the hybrid compounds showed better conformational fittings in the active site of the targeted proteins as compared to the parent ursolic acid. , Thesis (MSc) -- Faculty of Science and Agriculture, 2022
- Full Text:
- Date Issued: 2022
New thiazolidine-2,4-dione derivatives combined with organometallic ferrocene: Synthesis, structure and antiparasitic activity
- Oderinlo, Ogunyemi O, Tukulula, Matshawandile, Isaacs, Michelle, Taylor, Dale, Smith, Vincent J, Khanye, Setshaba D, Hoppe, Heinrich C
- Authors: Oderinlo, Ogunyemi O , Tukulula, Matshawandile , Isaacs, Michelle , Taylor, Dale , Smith, Vincent J , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122978 , vital:35382 , https://doi.org/10.1002/aoc.4385
- Description: Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.
- Full Text:
- Date Issued: 2018
- Authors: Oderinlo, Ogunyemi O , Tukulula, Matshawandile , Isaacs, Michelle , Taylor, Dale , Smith, Vincent J , Khanye, Setshaba D , Hoppe, Heinrich C
- Date: 2018
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/122978 , vital:35382 , https://doi.org/10.1002/aoc.4385
- Description: Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine (8a) and piperidine (8b) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b, which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.
- Full Text:
- Date Issued: 2018
On the ideals and semimodules of commutative semirings
- Authors: Olivier, Ruan
- Date: 2021-04
- Subjects: Gqeberha (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/52782 , vital:44026
- Description: Semirings are a generalisation of rings where additive inverses need not exist. In this dissertation, we focus on results of commutative semirings with non-zero identity. Many results that we study are analogous to results from commutative rings with non-zero identity. Properties which are unique to semirings are also investigated, such as semirings where all elements are additively idempotent. The notion of ideals is examined in the context of a semiring. Specifically, prime ideals, maximal ideals, k-ideals and partitioning ideals of semirings are considered. Additionally, the module over a ring is generalised to a semimodule over a semiring. The emphasis is on prime subsemimodules and multiplication semimodules. Lastly, invertible ideals of semirings are examined. , Thesis (MSc) -- Faculty of Science, School of Computer Science, Mathematics, Physics and Statistics, 2021
- Full Text:
- Date Issued: 2021-04
- Authors: Olivier, Ruan
- Date: 2021-04
- Subjects: Gqeberha (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/52782 , vital:44026
- Description: Semirings are a generalisation of rings where additive inverses need not exist. In this dissertation, we focus on results of commutative semirings with non-zero identity. Many results that we study are analogous to results from commutative rings with non-zero identity. Properties which are unique to semirings are also investigated, such as semirings where all elements are additively idempotent. The notion of ideals is examined in the context of a semiring. Specifically, prime ideals, maximal ideals, k-ideals and partitioning ideals of semirings are considered. Additionally, the module over a ring is generalised to a semimodule over a semiring. The emphasis is on prime subsemimodules and multiplication semimodules. Lastly, invertible ideals of semirings are examined. , Thesis (MSc) -- Faculty of Science, School of Computer Science, Mathematics, Physics and Statistics, 2021
- Full Text:
- Date Issued: 2021-04
Crystallographic Analysis and Structural Revision of a Spiroterpenoid Rearrangement Product
- Lobb, Kevin A, Kaye, Perry T
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2003
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449335 , vital:74812 , xlink:href="https://www.ajol.info/index.php/sajc/article/view/122435"
- Description: Single crystal X-ray analysis of a spiroterpenoid rearrangement product has revealed that its structure is, in fact, isomeric with the structure proposed previously – an observation that has significant mechanistic implications.
- Full Text:
- Date Issued: 2003
- Authors: Lobb, Kevin A , Kaye, Perry T
- Date: 2003
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/449335 , vital:74812 , xlink:href="https://www.ajol.info/index.php/sajc/article/view/122435"
- Description: Single crystal X-ray analysis of a spiroterpenoid rearrangement product has revealed that its structure is, in fact, isomeric with the structure proposed previously – an observation that has significant mechanistic implications.
- Full Text:
- Date Issued: 2003
Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial activity.
- Fomogne-Fodjo, M C Y, Ndinteh, Derek T, Olivier, Denise K, Krause, Rui W M, Kempgens, Pierre, Van Vuuren, S
- Authors: Fomogne-Fodjo, M C Y , Ndinteh, Derek T , Olivier, Denise K , Krause, Rui W M , Kempgens, Pierre , Van Vuuren, S
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125556 , vital:35795 , https://doi.org/10.1016/j.jep.2016.11.027
- Description: Ethnopharmacological relevance Tetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25 µg/mL) and M. aurum (65 µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne-Fodjo et al., 2014). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs.
- Full Text:
- Date Issued: 2017
- Authors: Fomogne-Fodjo, M C Y , Ndinteh, Derek T , Olivier, Denise K , Krause, Rui W M , Kempgens, Pierre , Van Vuuren, S
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125556 , vital:35795 , https://doi.org/10.1016/j.jep.2016.11.027
- Description: Ethnopharmacological relevance Tetracera potatoria Afzel. Exg. Don (Dilleniaceae) is a medicinal plant used traditionally in Africa for the treatment of tuberculosis related ailments and respiratory infections. The antibacterial activity of the medium polar extracts of T. potatoria leaves and stem bark was recently reported against Mycobacterium smegmatis (MIC 25 µg/mL) and M. aurum (65 µg/mL), two fast-growing Mycobacterium strains used as model micro-organisms for the more pathogenic strain Mycobacterium tuberculosis (Fomogne-Fodjo et al., 2014). The aim of this study was consequently to isolate the compounds possibly contributing to this activity, and which may therefore be promising precursors to be used for the development of novel anti-TB drugs.
- Full Text:
- Date Issued: 2017
Computational studies in human African trypanosomiasis
- Authors: Muronzi, Tendai
- Date: 2023-10-13
- Subjects: African trypanosomiasis , Apolipoprotein L1 , Docking , Protein-protein interactions , Homology modeling , Tetrahydrofolate dehydrogenase , Pteridine reductase
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431883 , vital:72812 , DOI 10.21504/10962/431885
- Description: Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) caused by two subspecies of the parasite, namely Trypanosoma brucei (Tb) gambiense (g-HAT) and rhodesiense (r-HAT). HAT is endemic in sub-Saharan countries, where the parasite transmission vectors, tsetse flies, breed. An estimated 70 million people remain at risk of contracting the disease, where the infection is classified as acute or chronic for g-HAT and r-HAT, respectively, with both forms ending in fatal meningoencephalitis when left untreated. Both g-HAT and r-HAT are responsible for widespread fatal epidemics throughout sub-Saharan African history, resulting from the complex molecular interplay between trypanosomes and humans through unique, innate immunity evasion mechanisms. Of interest, the Tbr subspecies expresses a serum resistance-associated protein (SRA), which binds to human serum lytic factor, apolipoprotein L1 (ApoL1), nullifying any trypanocidal activity. In response, ApoL1 (G1 and G2) variants found in humans of sub-Saharan African lineage have been cited for conferring resistance to the r-HAT infection in an interaction that is not fully elucidated In the event of successful infection, current HAT chemotherapeutics are plagued with complexity of administration, poor efficacy, toxicity, and potential drug resistance, highlighting a need for improved approaches. The parasite folate pathway provides a strategic target for alternative anti-trypanosomal drug development as trypanosomatids are folate auxotrophs, requiring host folate for growth and survival. Validated drug targets pteridine reductase (TbPTR1) and dihydrofolate reductase (TbDHFR) are essential for salvaging cofactors folate and folate biopterin crucial to parasite survival, making them viable targets for anti-folate investigation. The overall aims of this thesis were to a) provide insights into the molecular and dynamic basis of the SRA and ApoL1 interplay in HAT infection and b) identify safer and more efficient anti-folate anti-trypanosomal drug alternatives through in silico approaches. To achieve our first aim, in silico structure prediction was applied to generate 3D models of ApoL1 C-terminal variants G0, G1, G1G/M, G2 and G1G2, and four SRA variants retrieved from the NCBI database. The SRA and ApoL1 structures were inspected dynamically to identify the effect of the variants through molecular dynamics (MD) simulations. Dynamic residue network (DRN) analysis of MD trajectories was fundamental in identifying residues playing a vital role in the intramolecular communication of both proteins in the presence of mutations. Protein-protein docking was then applied to calculate plausible SRA-ApoL1 C-terminal wild-type complex structures to further elucidate the nature of SRA-mediated infection. Through MD simulations, twelve SRA-ApoL1 dimeric structures were narrowed down from five to two energetically sound complexes. The two feasible SRA-ApoL1 complexes (1 and 2) exhibited favourable communication observed through DRN analysis, including the retaining key communication residues identified in prior monomer DRN calculations. ApoL1 C-terminal variants were additionally incorporated into SRA-ApoL1 complexes 1 and 2 for further complex dynamics analysis This investigation into the nature of SRA-ApoL1 binding resulted in five primary outcomes: 1) highlighting the intramolecular effects ApoL1 variants have on the stability of the protein, 2) the identification of crucial SRA and ApoL1 communication residues in both monomeric or dimeric form, 3) the isolation of feasible SRA-ApoL1 complexes determined through global and local structural analyses 4) identification of residues crucial to the complex formation and maintenance of SRA-ApoL1, overlapping with those identified in (1), and 5) the minimal dissociative role of the G1 mutations in the complex, but compounding effect of the G2 deletion mutation. Computational modelling and drug repurposing were employed to achieve the thesis's second aim as they drastically cut down the costs involved in drug discovery and provide a more time-efficient screening method through numerous drug candidates. Using high throughput virtual screening, a subset of 2089 approved DrugBank compounds were screened against TbPTR1. The outputs were filtered to 24 viable compounds in 54 binding poses using binding energy and molecular interactions. Through subsequent MD simulations of 200ns, thirteen potential hit compounds were identified. The resultant hit compounds were subjected to further blind docking against TbDHFR and molecular dynamics to identify compounds with the potential for dual inhibition. The filtered subset was also tested in in vitro single concentration and dose-response bioassays to assess inhibitory properties against Trypanosoma brucei, complementing in silico findings. Post-molecular dynamics, four compounds exhibited high stabilities and molecular interactions with both TbPTR1 and TbDHFR, with two presenting favourable results in the in vitro assays. Three compounds additionally shared common structural moieties. In all, the in silico repurposing highlighted drugs characterised by favourable interactions and stabilities in TbPTR1, thus providing (1) a framework for further studies investigating anti-folate HAT compounds and (2) modulatory scaffolds based on identified moieties that can be used for the design of safe anti-folate trypanosomal drugs. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Muronzi, Tendai
- Date: 2023-10-13
- Subjects: African trypanosomiasis , Apolipoprotein L1 , Docking , Protein-protein interactions , Homology modeling , Tetrahydrofolate dehydrogenase , Pteridine reductase
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/431883 , vital:72812 , DOI 10.21504/10962/431885
- Description: Human African trypanosomiasis (HAT) is a neglected tropical disease (NTD) caused by two subspecies of the parasite, namely Trypanosoma brucei (Tb) gambiense (g-HAT) and rhodesiense (r-HAT). HAT is endemic in sub-Saharan countries, where the parasite transmission vectors, tsetse flies, breed. An estimated 70 million people remain at risk of contracting the disease, where the infection is classified as acute or chronic for g-HAT and r-HAT, respectively, with both forms ending in fatal meningoencephalitis when left untreated. Both g-HAT and r-HAT are responsible for widespread fatal epidemics throughout sub-Saharan African history, resulting from the complex molecular interplay between trypanosomes and humans through unique, innate immunity evasion mechanisms. Of interest, the Tbr subspecies expresses a serum resistance-associated protein (SRA), which binds to human serum lytic factor, apolipoprotein L1 (ApoL1), nullifying any trypanocidal activity. In response, ApoL1 (G1 and G2) variants found in humans of sub-Saharan African lineage have been cited for conferring resistance to the r-HAT infection in an interaction that is not fully elucidated In the event of successful infection, current HAT chemotherapeutics are plagued with complexity of administration, poor efficacy, toxicity, and potential drug resistance, highlighting a need for improved approaches. The parasite folate pathway provides a strategic target for alternative anti-trypanosomal drug development as trypanosomatids are folate auxotrophs, requiring host folate for growth and survival. Validated drug targets pteridine reductase (TbPTR1) and dihydrofolate reductase (TbDHFR) are essential for salvaging cofactors folate and folate biopterin crucial to parasite survival, making them viable targets for anti-folate investigation. The overall aims of this thesis were to a) provide insights into the molecular and dynamic basis of the SRA and ApoL1 interplay in HAT infection and b) identify safer and more efficient anti-folate anti-trypanosomal drug alternatives through in silico approaches. To achieve our first aim, in silico structure prediction was applied to generate 3D models of ApoL1 C-terminal variants G0, G1, G1G/M, G2 and G1G2, and four SRA variants retrieved from the NCBI database. The SRA and ApoL1 structures were inspected dynamically to identify the effect of the variants through molecular dynamics (MD) simulations. Dynamic residue network (DRN) analysis of MD trajectories was fundamental in identifying residues playing a vital role in the intramolecular communication of both proteins in the presence of mutations. Protein-protein docking was then applied to calculate plausible SRA-ApoL1 C-terminal wild-type complex structures to further elucidate the nature of SRA-mediated infection. Through MD simulations, twelve SRA-ApoL1 dimeric structures were narrowed down from five to two energetically sound complexes. The two feasible SRA-ApoL1 complexes (1 and 2) exhibited favourable communication observed through DRN analysis, including the retaining key communication residues identified in prior monomer DRN calculations. ApoL1 C-terminal variants were additionally incorporated into SRA-ApoL1 complexes 1 and 2 for further complex dynamics analysis This investigation into the nature of SRA-ApoL1 binding resulted in five primary outcomes: 1) highlighting the intramolecular effects ApoL1 variants have on the stability of the protein, 2) the identification of crucial SRA and ApoL1 communication residues in both monomeric or dimeric form, 3) the isolation of feasible SRA-ApoL1 complexes determined through global and local structural analyses 4) identification of residues crucial to the complex formation and maintenance of SRA-ApoL1, overlapping with those identified in (1), and 5) the minimal dissociative role of the G1 mutations in the complex, but compounding effect of the G2 deletion mutation. Computational modelling and drug repurposing were employed to achieve the thesis's second aim as they drastically cut down the costs involved in drug discovery and provide a more time-efficient screening method through numerous drug candidates. Using high throughput virtual screening, a subset of 2089 approved DrugBank compounds were screened against TbPTR1. The outputs were filtered to 24 viable compounds in 54 binding poses using binding energy and molecular interactions. Through subsequent MD simulations of 200ns, thirteen potential hit compounds were identified. The resultant hit compounds were subjected to further blind docking against TbDHFR and molecular dynamics to identify compounds with the potential for dual inhibition. The filtered subset was also tested in in vitro single concentration and dose-response bioassays to assess inhibitory properties against Trypanosoma brucei, complementing in silico findings. Post-molecular dynamics, four compounds exhibited high stabilities and molecular interactions with both TbPTR1 and TbDHFR, with two presenting favourable results in the in vitro assays. Three compounds additionally shared common structural moieties. In all, the in silico repurposing highlighted drugs characterised by favourable interactions and stabilities in TbPTR1, thus providing (1) a framework for further studies investigating anti-folate HAT compounds and (2) modulatory scaffolds based on identified moieties that can be used for the design of safe anti-folate trypanosomal drugs. , Thesis (PhD) -- Faculty of Science, Biochemistry and Microbiology, 2023
- Full Text:
- Date Issued: 2023-10-13
Cordidepsine is A Potential New Anti-HIV Depsidone from Cordia millenii
- Zeukang, Rostanie D, Siwe-Noundou, Xavier, Fotsing, Maurice T, Mbafor, Joseph T, Krause, Rui W M, Choudhary, Muhammad I, Atchade, Alex de Theodore
- Authors: Zeukang, Rostanie D , Siwe-Noundou, Xavier , Fotsing, Maurice T , Mbafor, Joseph T , Krause, Rui W M , Choudhary, Muhammad I , Atchade, Alex de Theodore
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193988 , vital:45413 , xlink:href="https://doi.org/10.3390/molecules24173202"
- Description: Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), β-amyrone (8), lupeol (9), β-amyrin (10), allantoin (11), 2′-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI–MS), high resolution electrospray ionization mass spectrometry (HR-ESI–MS), fast atom bombardment mass spectrometry (FAB–MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC50 = 4.65 μM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells.
- Full Text:
- Date Issued: 2019
- Authors: Zeukang, Rostanie D , Siwe-Noundou, Xavier , Fotsing, Maurice T , Mbafor, Joseph T , Krause, Rui W M , Choudhary, Muhammad I , Atchade, Alex de Theodore
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/193988 , vital:45413 , xlink:href="https://doi.org/10.3390/molecules24173202"
- Description: Chemical investigation of Cordia millenii, Baker resulted in the isolation of a new depsidone, cordidepsine (1), along with twelve known compounds including cyclooctasulfur (2), lup-20(29)-en-3-triacontanoate (3), 1-(26-hydroxyhexacosanoyl)glycerol (4), glyceryl-1-hexacosanoate (5) betulinic acid (6), lupenone (7), β-amyrone (8), lupeol (9), β-amyrin (10), allantoin (11), 2′-(4-hydroxyphenyl)ethylpropanoate (12) and stigmasterol glycoside (13). Hemi-synthetic reactions were carried out on two isolated compounds (5 and 6) to afford two new derivatives, that is, cordicerol A (14) and cordicerol B (15), respectively. The chemical structures of all the compounds were established based on analysis and interpretation of spectroscopic data such as electron ionization mass spectrometry (EI–MS), high resolution electrospray ionization mass spectrometry (HR-ESI–MS), fast atom bombardment mass spectrometry (FAB–MS), one dimension and two dimension nuclear magnetic resonance (1D and 2D-NMR) spectral data as well as X-ray crystallography (XRC). Lupeol ester derivatives [Lup-20(29)-en-3-triacontanoate (3)], monoglycerol derivatives [1-(26-hydroxyhexacosanoyl)glycerol (4) and glyceryl-1 hexacosanoate (5)] were isolated for the first time from Cordia genus while sulfur allotrope [cyclooctasulfur (2)] was isolated for the first time from plant origin. Biological assays cordidepsine (1) exhibited significant anti-HIV integrase activity with IC50 = 4.65 μM; EtOAc extract of stem barks, EtOAc fraction of roots and leaves were not toxic against 3T3 cells.
- Full Text:
- Date Issued: 2019
Synthesis, characterization and biological activity of some Dithiourea Derivatives:
- Odame, Felix, Hosten, Eric C, Krause, Jason, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Sayed, Yasien, Frost, Carminita L, Lobb, Kevin A, Tshentu, Zenixole R
- Authors: Odame, Felix , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
- Authors: Odame, Felix , Hosten, Eric C , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita L , Lobb, Kevin A , Tshentu, Zenixole R
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
The structure of aliphatic amine adducts of uranyl acetylacetonate. I. Dioxobis(2,4-pentanedionato)mono (2-N-methylaminopentan-4-one)uranium(VI)
- Haigh, John M, Nassimbeni, Luigi R, Pauptit, Richard A, Rodgers, Allen L, Sheldrick, George M
- Authors: Haigh, John M , Nassimbeni, Luigi R , Pauptit, Richard A , Rodgers, Allen L , Sheldrick, George M
- Date: 1976
- Subjects: Aliphatic amine adducts , Uranyl acetylacetonate
- Language: English
- Type: Article , text
- Identifier: vital:6373 , http://hdl.handle.net/10962/d1006077
- Description: Crystals of the title compound are monoclinic with a= 8.314 (5), b= 22.723 (9), c= 12.589 (6) A, /3= 123.0 (2t, Z=4, space group P2dc. The structure was determined by Patterson and Fourier methods and refined by full-matrix least squares to a final R of 0.030 for 2043 independent reflexions. The U atom has pentagonal bipyramidal coordination and the N-methylacetylacetoneamine is bonded to U via O. There are two intramolecular N-H. . .0 hydrogen bonds which govern the geometry of the adduct molecule.
- Full Text:
- Date Issued: 1976
- Authors: Haigh, John M , Nassimbeni, Luigi R , Pauptit, Richard A , Rodgers, Allen L , Sheldrick, George M
- Date: 1976
- Subjects: Aliphatic amine adducts , Uranyl acetylacetonate
- Language: English
- Type: Article , text
- Identifier: vital:6373 , http://hdl.handle.net/10962/d1006077
- Description: Crystals of the title compound are monoclinic with a= 8.314 (5), b= 22.723 (9), c= 12.589 (6) A, /3= 123.0 (2t, Z=4, space group P2dc. The structure was determined by Patterson and Fourier methods and refined by full-matrix least squares to a final R of 0.030 for 2043 independent reflexions. The U atom has pentagonal bipyramidal coordination and the N-methylacetylacetoneamine is bonded to U via O. There are two intramolecular N-H. . .0 hydrogen bonds which govern the geometry of the adduct molecule.
- Full Text:
- Date Issued: 1976
Rational design and regioselective synthesis of conformationally restricted furan-derived ligands as potential anti-malarial agents
- Mutorwa, Marius K, Nokalipa, Iviwe, Tanner, Delia C, Blatch, Gregory L, Lobb, Kevin A, Klein, Rosalyn, Kaye, Perry T
- Authors: Mutorwa, Marius K , Nokalipa, Iviwe , Tanner, Delia C , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447170 , vital:74589 , xlink:href="https://doi.org/10.24820/ark.5550190.p011.281"
- Description: Substituted 3-furanomethyl phosphate esters and their corresponding phosphoric acids have been prepared as conformationally restricted analogues of DOXP, the natural substrate for Plasmodium falciparum 1-deoxyD-xylulose-5-phosphate reductoisomerase (PfDXR), and fosmidomycin, an established inhibitor. Saturation Transfer Difference (STD) NMR analysis and in silico docking data suggest the potential of such compounds as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
- Authors: Mutorwa, Marius K , Nokalipa, Iviwe , Tanner, Delia C , Blatch, Gregory L , Lobb, Kevin A , Klein, Rosalyn , Kaye, Perry T
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/447170 , vital:74589 , xlink:href="https://doi.org/10.24820/ark.5550190.p011.281"
- Description: Substituted 3-furanomethyl phosphate esters and their corresponding phosphoric acids have been prepared as conformationally restricted analogues of DOXP, the natural substrate for Plasmodium falciparum 1-deoxyD-xylulose-5-phosphate reductoisomerase (PfDXR), and fosmidomycin, an established inhibitor. Saturation Transfer Difference (STD) NMR analysis and in silico docking data suggest the potential of such compounds as PfDXR inhibitors.
- Full Text:
- Date Issued: 2020
Tree species in unfamiliar places - Graaff-Reinet town
- Authors: Skead, C J (Cuthbert John)
- Date: 1959-06-10
- Subjects: Trees -- Graaff-Reinet, South Africa , Erythrina caffra -- Graaff-Reinet, South Africa , Cupressaceae -- Graaff-Reinet, South Africa , Afrocarpus falcatus -- Graaff-Reinet, South Africa
- Language: English
- Type: text , ephemera
- Identifier: http://hdl.handle.net/10962/65884 , vital:28854
- Description: Typed article regarding tree species found in Graaff-Reinet, East Cape Midlands. Trees mentioned include Erythrina caffra, cypresses and Yellowwood.
- Full Text:
- Date Issued: 1959-06-10
- Authors: Skead, C J (Cuthbert John)
- Date: 1959-06-10
- Subjects: Trees -- Graaff-Reinet, South Africa , Erythrina caffra -- Graaff-Reinet, South Africa , Cupressaceae -- Graaff-Reinet, South Africa , Afrocarpus falcatus -- Graaff-Reinet, South Africa
- Language: English
- Type: text , ephemera
- Identifier: http://hdl.handle.net/10962/65884 , vital:28854
- Description: Typed article regarding tree species found in Graaff-Reinet, East Cape Midlands. Trees mentioned include Erythrina caffra, cypresses and Yellowwood.
- Full Text:
- Date Issued: 1959-06-10
In vitro antimalarial, antitrypanosomal and HIV-1 integrase inhibitory activities of two Cameroonian medicinal plants
- Fouokeng, Yannick, Feumo Feusso, H M, Mbosso Teinkela, Jean E, Siwe-Noundou, Xavier, Wintjens, René T, Isaacs, Michelle, Hoppe, Heinrich C, Krause, Rui W M, Azébazé, Anatole G B, Vardamides, Juliette C
- Authors: Fouokeng, Yannick , Feumo Feusso, H M , Mbosso Teinkela, Jean E , Siwe-Noundou, Xavier , Wintjens, René T , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Azébazé, Anatole G B , Vardamides, Juliette C
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195014 , vital:45519 , xlink:href="https://doi.org/10.1016/j.sajb.2018.10.008"
- Description: Antiplasmodial, antitrypanosomal and anti-HIV-1 activities of crude extracts, fractions and some isolated compounds from two Cameroonian medicinal plants: Antrocaryon klaineanum Pierre (Anacardiaceae) and Diospyros conocarpa Gürke ex K. Schum. (Ebenaceae) were assessed. The phytochemical studies led to the isolation of eight compounds (1–8) from Diospyros conocarpa and six compounds (6, 9–13) from Antrocaryon klaineanum. These compounds were identified as mangiferolic acid (1), 3β, 22(S)-dihydroxycycloart-24E-en-26-oic acid (2), lupeol (3), aridanin (4), betulin (5), betulinic acid (6), bergenin (7), D-quercitol(8), entilin C(9), entilin A(10), antrocarine A(11), 7R,20(S)-dihydroxy-4,24(28)-ergostadien-3-one(12) and stigmasterol glucoside (13). The criteria for activity were set as follows: an IC50 value more than 10 μg/mL for crude extracts and more than 1 μg/mL for pure compounds. The hexane/ethyl acetate (1:1) fraction of A.klaineanum root bark (AKERF1) and the hexane/ethyl acetate (1:1) fraction of A.klaineanum trunk bark (AKETF1) presented the strongest antiplasmodial activities with IC50 values of 0.4 and 4.4 μg/mL, respectively. Aridanin (4) and antrocarine A(11), as well as the crude extract of D.conocarpa roots (EDCR), AKERF1 and AKETF1 showed moderate trypanocidal effects. The crude extract of A.klaineanum root bark (AKER) and AKETF1 exhibited attractive activities on HIV-1 integrase with IC50 values of 1.96 and 24.04 μg/mL, respectively. The results provide baseline information on the use of A.klaineanum and D.conocarpa extracts, as well as certain components, as sources of new antiplasmodial, antitrypanosomal and anti-HIV drugs.
- Full Text:
- Date Issued: 2019
- Authors: Fouokeng, Yannick , Feumo Feusso, H M , Mbosso Teinkela, Jean E , Siwe-Noundou, Xavier , Wintjens, René T , Isaacs, Michelle , Hoppe, Heinrich C , Krause, Rui W M , Azébazé, Anatole G B , Vardamides, Juliette C
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195014 , vital:45519 , xlink:href="https://doi.org/10.1016/j.sajb.2018.10.008"
- Description: Antiplasmodial, antitrypanosomal and anti-HIV-1 activities of crude extracts, fractions and some isolated compounds from two Cameroonian medicinal plants: Antrocaryon klaineanum Pierre (Anacardiaceae) and Diospyros conocarpa Gürke ex K. Schum. (Ebenaceae) were assessed. The phytochemical studies led to the isolation of eight compounds (1–8) from Diospyros conocarpa and six compounds (6, 9–13) from Antrocaryon klaineanum. These compounds were identified as mangiferolic acid (1), 3β, 22(S)-dihydroxycycloart-24E-en-26-oic acid (2), lupeol (3), aridanin (4), betulin (5), betulinic acid (6), bergenin (7), D-quercitol(8), entilin C(9), entilin A(10), antrocarine A(11), 7R,20(S)-dihydroxy-4,24(28)-ergostadien-3-one(12) and stigmasterol glucoside (13). The criteria for activity were set as follows: an IC50 value more than 10 μg/mL for crude extracts and more than 1 μg/mL for pure compounds. The hexane/ethyl acetate (1:1) fraction of A.klaineanum root bark (AKERF1) and the hexane/ethyl acetate (1:1) fraction of A.klaineanum trunk bark (AKETF1) presented the strongest antiplasmodial activities with IC50 values of 0.4 and 4.4 μg/mL, respectively. Aridanin (4) and antrocarine A(11), as well as the crude extract of D.conocarpa roots (EDCR), AKERF1 and AKETF1 showed moderate trypanocidal effects. The crude extract of A.klaineanum root bark (AKER) and AKETF1 exhibited attractive activities on HIV-1 integrase with IC50 values of 1.96 and 24.04 μg/mL, respectively. The results provide baseline information on the use of A.klaineanum and D.conocarpa extracts, as well as certain components, as sources of new antiplasmodial, antitrypanosomal and anti-HIV drugs.
- Full Text:
- Date Issued: 2019
Chemical analysis and biological activities of crude extracts and essential oil of selected medicinal plants from the Eastern Cape, South Africa, and Volta Region of Ghana
- Authors: Agbo, Irene Adzo
- Date: 2023-12
- Subjects: Medicinal plants , Lantana camara , Peptic ulcer -- Treatment , Traditional medicine - South Africa -- Eastern Cape , Traditional medicine -- Ghana
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/62431 , vital:72728
- Description: Lantana camara and Khaya grandifoliola extracts are among many plants found traditionally effective for the treatment of wounds and ulcers. This study assessed the phytochemical content, isolation and identification of single compounds from methanol and ethyl acetate extracts of Lantana camara and Khaya grandifoliola. Further, the bioactivity testing including antioxidant, antimicrobial and cytoxicity of the extracts was done to confirm the wound healing potential discovered by the traditional healers. Materials and methods: Extraction was done successively using maceration method with 100 % ethyl acetate and 100 % methanol with a biomass-to-solvent ratio of 1:3 (w/v) to obtain L. camara ethyl acetate extracts of berry (ELB), flower (ELF) and leaf (ELL) and methanol extracts of MLB, MLF, MLL and K. grandifoliola ethyl acetate extracts of leaf (EKL), root (EKR) and stem bark (EKSB) and methanol extracts of MKL, MKR, MKSB respectively. L. camara leaf essential oil (EO) was extracted using the hydro-distillation method with a Clevenger apparatus. Total phytochemical content was assessed for each extract using spectrophotometric methods and a calibration curve of standards: bromocresol green method with atropine; Folin–Ciocalteu colorimetric method with gallic acid, aluminium chloride colorimetric method with quercetin and concentrated sulphuric acid chloroform with linalool for total alkaloid, phenolic, flavonoid and terpenoid contents respectively. Single compound isolation and purification was conducted using chromatographic techniques. Elucidation of single compounds was done using spectrometric method, high resolution- mass spectrometry, and one and two-dimensional (1D and 2D)-NMR. Stereochemistry of each compound was confirmed using electronic circular dichroism spectra. A Crystalline compound was identified by single crystal X-ray diffraction using CuKα-radiation. In vitro bioactivities were assessed with methods such as 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide, free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl, inhibitory effect on nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages, and 96-well plate micro dilution for cytotoxicity, ant-inflammatory and antimicrobial activity testing. Results: Methanol extracts of both plants retained high phytochemical concentrations of all the phytoconstituents investigated compared with the ethyl acetate extracts which retained lower concentrations. The results of the L. camara methanol extracts include; total alkaloid content (TAC) (2.05±0.18, 1.87±1.54 and 2.60±1.10 mg AEQ/100 mg); total phenolic content (TPC) (14.05±4.04, 34.59±3.01 and 18.58±1.87 mg GAEQ/100 mg); the total flavonoid content(TFC) of flower (12.45±1.87, 20.41±2.69 and mg QEQ/100 mg); total terpenoids (TTC) (20.74±2.34, 20.74±2.34 and 15.97±1.19 mg LIN EQ/100mg) of MLB, MLF and MLL respectively. Whereas that of the K. grandifoliola methanol extracts include; TAC (7.32±0.14,8.49±0.34, 10.67±0.22 mg AEQ/100 mg); TPC (37.49±1.40, 44.41±0.69, 53.57±1.50 mgGAEQ/100 mg); TFC (6.54±0.55, 9.58±0.89 and 10.26±0.92 mg QEQ/100 mg); TTC(10.16±1.41, 35.78±2.14 and 23.45±1.76 mg LIN EQ/100mg) of MKL, MKR and MKSB respectively. The major components of essential oil, out of the 71 constituents identified include Davanone D (32.91 %), Caryophyllene (5.07 %), Nerolidol 2 (3.56 %) and GermacreneD (3.13 %). Compounds 3.47 was isolated from the methanol extract of L. camara flowers. This compound is reported for the first time from the L. camara flower extract. Two compounds, compounds 4.23, and 4.26, were isolated from the methanol extract of K. grandifoliola roots, compound 4.22 was isolated from the ethyl acetate root extract while compounds 4.24 and 4.25 were isolated from the ethyl acetate stem bark extract as isomers in a mixture. Compounds 4.22 and 4.23 are reported from K. grandifoliola root for the first time. The isolated compounds (compounds 3.47 and 4.23) were nontoxic to the Vero cell line and this may contribute to possible stimulation of cell proliferation, promoting wound healing. Cytotoxicity describes extract virulence to Vero cell line. MLF and ELB were found nontoxic even at the highest concentration of 200 μg/mL. The MKSB and MKR, as well as the EKSB were nontoxic. Antioxidant activity results, described by the percentage inhibition in the DPPH assay, showed that MLF and MKSB had the highest antioxidant activities compared with the ascorbic acid standard, with IC50 of 38.68±5.09 and 37.03±11.95 μg/mL for L. camara and K. grandifoliola respectively. ELB exhibited a significant anti-inflammatory activity inhibiting NO• radical generation in the LPS-stimulated RAW 264.7 macrophages at concentration ranging from 50 and 100 μg/mL. EKSB and MKR showed significant anti-inflammatory activity at 100 and 200 μg/ml respectively. ELL and ELF demonstrated potent growth inhibition against S. pyogenes with an MIC value ≤ 0.125 mg/mL, while the MICs of the ELB and MLL were 0.5 mg/mL and 2 mg/mL respectively. MKSB and MKR and EKSB extract exhibited an effective growth inhibition against S. aureus with MIC of 1 mg/mL. The growth of S. pyogenes was supressed by both ethyl acetate and methanol extracts of all plant parts tested with MIC ranging from 0.25–2 mg/mL. Conclusion: The potent bioactivity shown in the results of the cytotoxicity, antioxidant activity, anti-inflammatory and antimicrobial activity testing, and the nontoxic singlecompounds of L. camara and K. grandifoliola extracts led to the conclusion that the two plants had wound healing potential. The study therefore confirmed their traditional uses for treatment of wounds. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2023
- Full Text:
- Date Issued: 2023-12
- Authors: Agbo, Irene Adzo
- Date: 2023-12
- Subjects: Medicinal plants , Lantana camara , Peptic ulcer -- Treatment , Traditional medicine - South Africa -- Eastern Cape , Traditional medicine -- Ghana
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10948/62431 , vital:72728
- Description: Lantana camara and Khaya grandifoliola extracts are among many plants found traditionally effective for the treatment of wounds and ulcers. This study assessed the phytochemical content, isolation and identification of single compounds from methanol and ethyl acetate extracts of Lantana camara and Khaya grandifoliola. Further, the bioactivity testing including antioxidant, antimicrobial and cytoxicity of the extracts was done to confirm the wound healing potential discovered by the traditional healers. Materials and methods: Extraction was done successively using maceration method with 100 % ethyl acetate and 100 % methanol with a biomass-to-solvent ratio of 1:3 (w/v) to obtain L. camara ethyl acetate extracts of berry (ELB), flower (ELF) and leaf (ELL) and methanol extracts of MLB, MLF, MLL and K. grandifoliola ethyl acetate extracts of leaf (EKL), root (EKR) and stem bark (EKSB) and methanol extracts of MKL, MKR, MKSB respectively. L. camara leaf essential oil (EO) was extracted using the hydro-distillation method with a Clevenger apparatus. Total phytochemical content was assessed for each extract using spectrophotometric methods and a calibration curve of standards: bromocresol green method with atropine; Folin–Ciocalteu colorimetric method with gallic acid, aluminium chloride colorimetric method with quercetin and concentrated sulphuric acid chloroform with linalool for total alkaloid, phenolic, flavonoid and terpenoid contents respectively. Single compound isolation and purification was conducted using chromatographic techniques. Elucidation of single compounds was done using spectrometric method, high resolution- mass spectrometry, and one and two-dimensional (1D and 2D)-NMR. Stereochemistry of each compound was confirmed using electronic circular dichroism spectra. A Crystalline compound was identified by single crystal X-ray diffraction using CuKα-radiation. In vitro bioactivities were assessed with methods such as 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide, free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl, inhibitory effect on nitric oxide production in lipopolysaccharide-activated RAW 264.7 macrophages, and 96-well plate micro dilution for cytotoxicity, ant-inflammatory and antimicrobial activity testing. Results: Methanol extracts of both plants retained high phytochemical concentrations of all the phytoconstituents investigated compared with the ethyl acetate extracts which retained lower concentrations. The results of the L. camara methanol extracts include; total alkaloid content (TAC) (2.05±0.18, 1.87±1.54 and 2.60±1.10 mg AEQ/100 mg); total phenolic content (TPC) (14.05±4.04, 34.59±3.01 and 18.58±1.87 mg GAEQ/100 mg); the total flavonoid content(TFC) of flower (12.45±1.87, 20.41±2.69 and mg QEQ/100 mg); total terpenoids (TTC) (20.74±2.34, 20.74±2.34 and 15.97±1.19 mg LIN EQ/100mg) of MLB, MLF and MLL respectively. Whereas that of the K. grandifoliola methanol extracts include; TAC (7.32±0.14,8.49±0.34, 10.67±0.22 mg AEQ/100 mg); TPC (37.49±1.40, 44.41±0.69, 53.57±1.50 mgGAEQ/100 mg); TFC (6.54±0.55, 9.58±0.89 and 10.26±0.92 mg QEQ/100 mg); TTC(10.16±1.41, 35.78±2.14 and 23.45±1.76 mg LIN EQ/100mg) of MKL, MKR and MKSB respectively. The major components of essential oil, out of the 71 constituents identified include Davanone D (32.91 %), Caryophyllene (5.07 %), Nerolidol 2 (3.56 %) and GermacreneD (3.13 %). Compounds 3.47 was isolated from the methanol extract of L. camara flowers. This compound is reported for the first time from the L. camara flower extract. Two compounds, compounds 4.23, and 4.26, were isolated from the methanol extract of K. grandifoliola roots, compound 4.22 was isolated from the ethyl acetate root extract while compounds 4.24 and 4.25 were isolated from the ethyl acetate stem bark extract as isomers in a mixture. Compounds 4.22 and 4.23 are reported from K. grandifoliola root for the first time. The isolated compounds (compounds 3.47 and 4.23) were nontoxic to the Vero cell line and this may contribute to possible stimulation of cell proliferation, promoting wound healing. Cytotoxicity describes extract virulence to Vero cell line. MLF and ELB were found nontoxic even at the highest concentration of 200 μg/mL. The MKSB and MKR, as well as the EKSB were nontoxic. Antioxidant activity results, described by the percentage inhibition in the DPPH assay, showed that MLF and MKSB had the highest antioxidant activities compared with the ascorbic acid standard, with IC50 of 38.68±5.09 and 37.03±11.95 μg/mL for L. camara and K. grandifoliola respectively. ELB exhibited a significant anti-inflammatory activity inhibiting NO• radical generation in the LPS-stimulated RAW 264.7 macrophages at concentration ranging from 50 and 100 μg/mL. EKSB and MKR showed significant anti-inflammatory activity at 100 and 200 μg/ml respectively. ELL and ELF demonstrated potent growth inhibition against S. pyogenes with an MIC value ≤ 0.125 mg/mL, while the MICs of the ELB and MLL were 0.5 mg/mL and 2 mg/mL respectively. MKSB and MKR and EKSB extract exhibited an effective growth inhibition against S. aureus with MIC of 1 mg/mL. The growth of S. pyogenes was supressed by both ethyl acetate and methanol extracts of all plant parts tested with MIC ranging from 0.25–2 mg/mL. Conclusion: The potent bioactivity shown in the results of the cytotoxicity, antioxidant activity, anti-inflammatory and antimicrobial activity testing, and the nontoxic singlecompounds of L. camara and K. grandifoliola extracts led to the conclusion that the two plants had wound healing potential. The study therefore confirmed their traditional uses for treatment of wounds. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2023
- Full Text:
- Date Issued: 2023-12